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Differential metabolite screening Under the threshold, a total of 1150 significantly differential metabolites were identified between HN and LN groups, such as cotinine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL)-N-glucuronide, 1-(5'-phosphoribosyl)-5-formamido-4-imidazolecarboxamide, 1-methylxanthine, 1,2-dihydroxy-3-keto-5-methylthiopentene, 11-dehydro-thromboxane B2, 2-hydroxyethanesulfonate, 2-hydroxyfelbamate, 2-methoxyestrone 3-glucuronide, deoxycholic acid 3-glucuronide, 2-phenylethanol glucuronide, and pregnanediol 3-O-glucuronide (Supplementary file Table S4)

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A key finding of our analysis was that one of the five TTCs was dominant in 77 out of the 90 countries analyzed